Our goal was to examine the causal link between blood metabolites, their ratios, and the risk of developing proliferative diabetic retinopathy (PDR) from a genetic insight. Summary-level data about 1400 blood metabolites and their ratios, as well as PDR, were sourced from prior genome-wide association studies (GWAS). A two-sample univariate and multivariate Mendelian randomization (MR) approach was utilized. Additionally, metabolic pathway analysis and sensitivity analysis were also conducted. After adjusting for multiple tests, four blood metabolites significantly correlated with PDR risk. Two ceramides, including glycosyl-N-palmitoyl-sphingosine (d18:1/16:0) (odds ratio [OR] = 1.12, 95% confidence interval (CI): 1.06-1.17, < 0.001, false discovery rate (FDR) = 0.005) and glycosyl-N-behenoyl-sphingadienine (d18:2/22:0) (OR = 1.11, 95% CI: 1.06-1.16, < 0.001, FDR = 0.017), were linked to increased risk. Additionally, 3-methylcytidine (OR = 1.05, 95% CI: 1.03-1.08, < 0.001, FDR = 0.021) also posed a risk, whereas (N(1)+N(8))-acetylspermidine (OR = 0.91, 95% CI: 0.87-0.94, < 0.001, FDR = 0.002) appeared protective. Multivariable MR analysis further confirmed a direct, protective effect of (N(1)+N(8))-acetylspermidine on PDR risk (OR = 0.94, 95% CI: 0.89-1.00, = 0.040). The sensitivity analysis results indicated that evidence for heterogeneity and pleiotropy was absent. These metabolites have the potential to be used as biomarkers and are promising for future research into the mechanisms and drug targets for PDR.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540900PMC
http://dx.doi.org/10.1155/2024/6828908DOI Listing

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